Establishment and analysis of chronic rejection model of mouse heart transplantation

Objective Establish a chronic rejection (CR) model of mouse heart transplantation and analyze its characteristics.

Methods Allogeneic Balb/c and C57BL/6 mice were used as donor and recipient for heart transplantation, and intraperitoneal injection of cytotoxic T lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig) was given 1 and 2 days after surgery. Graft survival time, donor specific antibody (DSA) level, graft pathology and inflammatory cell infiltration were observed.

Results In allogeneic transplantation model, graft survival time was prolonged after CTLA4-Ig treatment (28.2±4.1) d vs. (7.0±0.7) d, P < 0.01. The level of serum DSA-IgG increased at 2, 3 and 4 weeks after surgery, while the level of DSA-IgM remained unchanged. Myocardial cell injury, inflammatory cell infiltration, interstitial fibrosis and C4d deposition in capillaries were aggravated 3 weeks after operation. And it worsened 4 weeks after operation. The infiltrated immune cells were mainly macrophages, T cells and plasma cells.

Conclusions In this study, mouse allogeneic heart transplantation combined with CTLA4-Ig successfully established a CR model, which provided a basis for subsequent studies on the pathogenesis and intervention of CR.